Tailoring swelling to control softening mechanisms during cyclic loading of PEG/cellulose hydrogel composites

One of the novel approaches for discogenic lower back pain treatment is to permanently replace the core of the intervertebral disc, so-called Nucleus Pulposus, through minimally invasive surgery. Recently, we have proposed Poly(Ethylene Glycol) Dimethacrylate (PEGDM) hydrogel reinforced with Nano-Fibrillated Cellulose (NFC) fibers as an appropriate replacement material. In addition to the tuneable properties, that mimic those of the native tissue, the surgeon can directly inject it into the degenerated disc and cure it in situ via UV-light irradiation. However, in view of clinical applications, the reliability of the proposed material has to be tested under long-term fatigue loading. To that end, the present study focused on the characterization of the fatigue behavior of the composite hydrogel and investigated the governing physical phenomena behind it. The results show that composite PEGDM-NFC hydrogel withstands the 10 million compression cycles at physiological condition. However, its modulus decreases by almost 10% in the first cycle and then remains constant, while cyclic loading does not affect the neat PEGDM hydrogel. The observed softening behavior has similar characteristics of the Mullins effect. It is shown that the reduction of modulus is due to the gradual change of NFC network, which is highly stretched in the swollen state. Moreover, the swelling degree of the matrix is correlated to the extent of softening during cyclic loading. Consequently, softening can be minimized by lowering the swelling of the composite hydrogel.

Hybrid hydrogels for load-bearing implants

Céline Samira Wyss

Load-bearing tissues such as articular cartilage or meniscus are not infallible. They might fail due to trauma, over-solicitations, or diseases, which could subsequently alter the mobility of the patient. Repairing these damaged tissues in a minimally invasive way is nowadays widely studied. Hydrogels are promising for repairing soft tissues. However, trying to reproduce the highly hierarchical microstructures of load-bearing tissues is extremely complicated. In fact, conceiving hydrogels with optimal properties for specific applications is challenging as most of the hydrogel's properties are interrelated, such as toughness, stiffness, swelling, or deformability. The improvement of one property usually comes at the cost of another. This thesis aims to develop different hydrogel microstructures and evaluate their potential for load-bearing implants. In particular, the study focuses on (i) designing tough and fatigue resistant hydrogels, (ii) establishing a methodology to control the stiffness and the swelling of hydrogels independently, and (iii) considering processing ease by tailoring each hydrogel precursor viscosity. An extensive parametric study on hydrogels' structure and composition allowed establishing complete property charts for mechanical, swelling, and rheological properties. Seven different hydrogel structures based on poly(ethylene glycol) dimethacrylate were developed: neat, double network, composite, double network composite, granular, hybrid granular, and silk granular hydrogels. The precursors of neat hydrogels had the lowest viscosity. Microgels of similar composition were added to the precursor to adapt and increase its viscosity for unconfined applications. In parallel, adding nano-fibrillated cellulose fibers was effective for increasing toughness. This method was more efficient than creating a double network with alginate. Moreover, fatigue tests revealed that hydrogel composites successfully survive 10 million loading cycles at 20% applied strain. However, it became softer after the first loading cycles and behaved similarly to the Mullins effect. Subsequently, we assessed how cyclic loading affects fracture behavior, distribution of strain fields, and microstructure. The study demonstrated that cyclic loading on hydrogel composites re-arrange the fiber network without seriously deteriorating the mechanical properties. Additionally, we demonstrated that combining composite and microgel approaches, i.e. hybrid granular hydrogels, effectively tailored hydrogels' swelling and viscosity without significantly affecting stiffness, toughness, and deformability. Finally, the microgels were swollen in silk fibroin solution for forming self-reinforced silk granular hydrogels. Those hydrogels exhibited considerably higher stiffness and lower swelling but also reduced elongation performances. We demonstrated that hydrogels' mechanical and physical properties could be effectively controlled with the microstructures and compositions of well-known biomaterials. Subsequently, a hydrogel composite and a silk granular hydrogel, based this time on gelatin hydrogels, were synthesized, validating the potential of studied structures with other hydrogels and microgels. Finally, the analyzed material systems can be combined through a sequential layering, forming hybrid hydrogels, to obtain local or gradient properties addressing specific biomedical applications, soft robotics, sensing applications, or even food packaging.

EPFL2021

Nano Fibrillated Cellulose Based Composite Hydrogels for an Injectable Intervertebral Disc Implant

Azadeh Khoushabi

Replacing the gel-like central part of the intervertebral disc (IVD), so-called nucleus pulposus (NP), via a minimally invasive surgery is one of the most recent approaches in the lower back pain treatments. An appropriate biomaterial for NP replacement (NPR) preferably possesses the mechanical and swelling properties similar to those of the native tissue. Furthermore, it should be injectable, biocompatible and stable in the IVD environment. From the surgical point of view, employing a photopolymerizable hydrogel for NPR is beneficial as it can be injected in the liquid form to the IVD and subsequently cured in situ. Such an approach provides a better control for the surgeon over the operation and minimizes the invasion of the surrounding tissue. The application of hydrogels as load-bearing biomedical components is, however, limited by their mechanical properties. Conventional approaches to address such an issue often favors one mechanical property while compromising the others. The present study aims to develop a novel injectable, photopolymerizable hydrogel for NPR with concurrently enhanced mechanical properties and optimal processability. Hydrogels based on photopolymerization of a monomer, i.e. N-vinyl-2-pyrrolidone (NVP), and cross-linking of a preformed functionalized polymer, i.e. poly(ethylene glycol)dimethacrylate (PEGDM), are synthesized. The hydrogels are thoroughly characterized as a function of cross-link density and initial water content in order to examine their applicability for NPR. While a wide range of properties is obtained by variation of the aforementioned parameters, an enhancement of stiffness is associated with brittleness or loss of water content. In addition, homogenous volumetric photopolymerization of such hydrogels is found to be limited especially in case of local illumination. To resolve such issues, a composite material design approach is adopted and the abovementioned polymer networks of hydrogels are combined with nano fibrillated cellulose (NFC). It is demonstrated that the NFC significantly increases the hydrogelsâ stiffness (up to 275%) without compromising the failure strength or reducing the water content. Moreover, the NFC fibers effectively prevent formation of the swelling induced cracks in the NVP based hydrogels. The results of rheology experiments indicate that the dispersed NFC fibers form a network-like structure in the hydrogels precursor solution. Such a structure, as confirmed through the photorheology tests, serves as a light-scattering source when the solution is illuminated by UV light. The latter accelerates the kinetics of photopolymerization and consequently allows reducing the required concentration of photoinitiator. The enhanced and tunable properties of the PEGDM-NFC composite hydrogel, developed in this work, make it a promising implant material for NPR. The applicability and reliability of such a material design approach for NPR is examined using a bovine organ model. In order to meet the properties of the native tissue, the mechanical properties of the composite hydrogel are tuned. The performance of the optimized composite hydrogel versus the native NP tissue is evaluated in several functional tests such as extrusion, confined compression and swelling pressure...

EPFL2016

Structure et mécanismes de microdéformation de polymethylmethacrylates renforcés au choc

Laure Dupuits Lalande

Polymethylmethacrylate (PMMA) is used in many applications requiring good optical properties, resistance to ageing and resistance to UV irradiation, in spite of its relatively poor mechanical response to impact loading. In order to extend the range of application of this transparent but fragile material, and improve its competitiveness with engineering polymers such as polycarbonate, it is necessary to improve its fracture resistance. Several generations of toughened PMMA reinforced by addition of rubber particles have therefore been developed by Arkema over the last decade ("rubber toughened PMMA" (RTPMMA)). However, there remains a need for substantial improvement even in these relatively fracture resistant materials, providing the overall motivation for this project. The first type of material considered is based on RTPMMA in which the matrix ductility has been improved by copolymerization with up to 25 % ethyl acrylate (EA). The reinforcing particles used in these new modified RTPMMA grades comprise a PMMA core, either one (conventional 3L particles), or two rubbery layers (experimental 4L particles), and finally an outer grafted PMMA shell. A second, entirely new type of rubber modified PMMA, based on Poly(MMABA-MMA) copolymers (MAM) prepared by controlled radical polymerization (PRC) is then considered. PRC is carried out using nitroxide initiators, making it possible to polymerize the blocks of PMMA from the blocks of PBA in a continuous mass process. Although little was known about their mechanical response prior to the present work, the MAM copolymers represent an attractive alternative to RTPMMA from an economic point of view since their production involves essentially only one step. The scientific aim of this study is to understand the relationship between the mechanical properties, the crack propagation mechanisms and the microstructure of these various impact reinforced PMMA materials, and, if possible, to use this knowledge to identify strategies for improving their performance. It is first shown that there is an increase in the strain to break from 10 % to up to 30 % on addition of 25 % EA to the PMMA matrix, and a corresponding reduction in the yield stress from 95 to 60 MPa. The TEM observations of thin films deformed in-situ show these changes to be associated with a change in microdeformation mechanism from crazing in the pure PMMA to homogeneous plastic deformation. However, they are not accompanied by any substantial improvement in the high speed fracture resistance, the value of the maximum stress intensity factor, KImax, at 1 m/s remaining at about 2 MPa.m1/2 in all the matrices investigated. The ductility improves significantly on addition of the 3L and 4L particles, and this improvement is particularly marked with the 4L particles, the strain to break reaching 80 % and the yield stress dropping to about 40 MPa, regardless of the matrix EA content. The fracture resistance also increases over the full range of speeds investigated, and optimum performance is obtained in the matrix containing 25 % EA combined with 4L particles, KImax ranging from 3.2 MPa.m1/2 at 10-4 m/s to 3.5 MPa.m1/2 at 1 m/s. At low speeds, both the 3L and 4L particles deform by cavitation of the rubbery layer and, as the EA content is raised, the matrix microdeformation mechanism at the crack tip changes from crazing to simple shear, consistent with the observations for the matrix. Nevertheless, at very high speeds, at which crazing dominates in all the materials, the rubbery phase of the particles is argued to become relatively rigid and hence increasingly ineffective in decreasing the crack propagation energy. Thus, the overall improvements in mechanical behaviour obtained on EA addition are not reflected by an improvement in the notched Charpy impact toughness, which does not exceed 5.5 kJ/m2 in any of the RTPMMA. There may be scope for further optimizing the particle size at high EA contents owing to an observed decrease in entanglement molar mass, as demonstrated in previous work by Béguelin et al., but this is not thought to be viable from an economic point of view. MAM copolymers provide an alternative, low cost means of introducing a rubbery phase with controlled dimensions and morphology into a PMMA matrix. These MAM copolymers show similar ductility in tension to the RTPMMA (strain to break around 70 %) and an even lower yield stress (around 25 MPa depending on the grade). MAM is found to show a lamellar morphology for PMMA contents, ∫PMMA < 75%, and deformation of this morphology results in extension of the PBA phase and formation of chevron-like regions of shear deformation. Even so, the fracture resistance remains relatively low in the first generation of these materials, KImax not exceeding 2 MPa.m1/2 at 1 m/s, and Charpy impact tests on notched samples showing relatively little improvement between MAM and the PMMA homopolymer (notched Charpy impact toughness of up to 2.25 kJ/m2 compared with 1 kJ/m2 for PMMA and 5.5 kJ/m2 for RTPMMA). The morphological observations and mechanical test results for MAM nevertheless point to the important role of the molar mass and ∫PMMA, and also to the interest of stripping, i.e. removal of residual BA monomer prior to polymerization of the MMA block. It has hence been possible to design and produce a second generation of stripped MAM copolymers with higher molar masses (Mn > 100 kg/mol) and an optimum ∫PMMA (< 65 %). These are found not only to show ductile behaviour in tension and excellent optical properties, but also notched Charpy impact toughnesses approaching 6 kJ/m2. Although this is still significantly less than for polycarbonate (12 kJ/m2), it demonstrates the promise of MAM for expanding the range of applications of MMA-based systems beyond that currently accessible to conventional RTPMMA.

EPFL2007